Inclusion of sorghum, millet and cottonseed meal in broiler diets: a meta-analysis of effects on performance.
A meta-analysis was conducted (i) to evaluate broiler response to partial or total substitution of corn by sorghum and millet and (ii) to determine the effect of soybean meal replacement by cottonseed meal in broiler diet. The database included 190 treatments from 29 experiments published from 1990 to 2013. Bird responses to an experimental diet were calculated relative to the control (Experimental-Control), and were submitted to mixed-effect models. Results showed that diets containing millet led to similar performance as the corn-based ones for all parameters, whereas sorghum-based diets decreased growth performance. No major effect of the level of substitution was observed with millet or cottonseed meal. No effect of the level of substitution of sorghum on feed intake was found; however, growth performance decreased when the level of substitution of corn by sorghum increased. Cottonseed meal was substituted to soybean meal up to 40% and found to increase feed intake while reducing growth performance. Young birds were not more sensitive to these ingredients than older birds since there was no negative effect of these ingredients on performance in the starter phase. Results obtained for sorghum pointed out the necessity to find technological improvements that will increase the utilization of these feedstuffs in broiler diet. An additional work is scheduled to validate these statistical results in vivo and to evaluate the interactions induced with the simultaneous inclusions of sorghum, millet and cottonseed meal in broiler feeding.


A microscale soft ionic power source modulates neuronal network activity.
Bio-integrated devices need power sources to operate1,2. Despite widely used technologies that can provide power to large-scale targets, such as wired energy supplies from batteries or wireless energy transduction3, a need to efficiently stimulate cells and tissues on the microscale is still pressing. The ideal miniaturized power source should be biocompatible, mechanically flexible and able to generate an ionic current for biological stimulation, instead of using electron flow as in conventional electronic devices4-6. One approach is to use soft power sources inspired by the electrical eel7,8; however, power sources that combine the required capabilities have not yet been produced, because it is challenging to obtain miniaturized units that both conserve contained energy before usage and are easily triggered to produce an energy output. Here we develop a miniaturized soft power source by depositing lipid-supported networks of nanolitre hydrogel droplets that use internal ion gradients to generate energy. Compared to the original eel-inspired design7, our approach can shrink the volume of a power unit by more than 105-fold and it can store energy for longer than 24 h, enabling operation on-demand with a 680-fold greater power density of about 1,300 W m-3. Our droplet device can serve as a biocompatible and biological ionic current source to modulate neuronal network activity in three-dimensional neural microtissues and in ex vivo mouse brain slices. Ultimately, our soft microscale ionotronic device might be integrated into living organisms.


Increased intracellular calcium and decreased activities of leucocyte Na+,K+-ATPase and Ca2+-ATPase in asthma.
The present study was carried out to determine the intracellular free calcium concentration ([Ca(2+)](i)) and the activity of its regulatory enzymes (Na(+),K(+)-ATPase and Ca(2+)-ATPase) in leucocytes. Levels of plasma lysophosphatidylcholine (LPC) were also measured. Then the relationship between these parameters and the clinical severity of asthma and bronchial reactivity was studied. Patients with asthma were divided into three groups: acute asthma (subjects in acute exacerbation), uncontrolled asthma (subjects currently symptomatic) and stable asthma (subjects currently asymptomatic). A group of normal subjects was also studied. Spirometry, specific airway conductance and bronchial reactivity measurements were carried out. The following biochemical parameters were studied in venous blood: leucocyte [Ca(2+)](i), Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, and plasma LPC. Leucocyte [Ca(2+)](i) was increased and the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase were decreased in patients with asthma. Plasma levels of LPC were also increased. These changes were observed to be greatest among asthmatics in acute exacerbation of asthma, and lesser in magnitude in patients with less severe asthma. The activities of both ATPases were found to have a significant positive correlation, and [Ca(2+)](i) and the levels of plasma LPC a significant negative correlation, with predicted forced expiratory volume in 1 s (FEV(1)). No significant correlation was observed between the biochemical parameters and bronchial reactivity. It is concluded that intracellular calcium homoeostasis is abnormal in asthma; specifically, the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase are decreased. These abnormalities may modulate the clinical severity of asthma.


Do we still need breast cancer screening in the era of targeted therapies and precision medicine?
Breast cancer (BC) is the most common female cancer and the second cause of death among women worldwide. The 5-year relative survival rate recently improved up to 90% due to increased population coverage and women's attendance to organised mammography screening as well as to advances in therapies, especially systemic treatments. Screening attendance is associated with a mortality reduction of at least 30% and a 40% lower risk of advanced disease. The stage at diagnosis remains the strongest predictor of recurrences. Systemic treatments evolved dramatically over the last 20 years: aromatase inhibitors improved the treatment of early-stage luminal BC; targeted monoclonal antibodies changed the natural history of anti-human epidermal growth factor receptor 2-positive (HER2) disease; immunotherapy is currently investigated in patients with triple-negative BC; gene expression profiling is now used with the aim of personalising systemic treatments. In the era of precision medicine, it is a challenging task to define the relative contribution of early diagnosis by screening mammography and systemic treatments in determining BC survival. Estimated contributions before 2000 were 46% for screening and 54% for treatment advances and after 2000, 37% and 63%, respectively. A model showed that the 10-year recurrence rate would be 30% and 25% using respectively chemotherapy or novel treatments in the absence of screening, but would drop to 19% and 15% respectively if associated with mammography screening. Early detection per se has not a curative intent and systemic treatment has limited benefit on advanced stages. Both screening mammography and systemic therapies continue to positively contribute to BC prognosis.


Wilfoside K1N isolated from Cynanchum wilfordii inhibits angiogenesis and tumor cell invasion.
Wilfoside K1N is a polyoxypregnane glycoside isolated from Cynanchum wilfordii (Asclepiadaceae). Polyoxypregnane glycosides are associated with cellular immunity and anti-tumor activity, and increase the cytotoxicity of many anti-cancer drugs showing multidrug resistant activity on tumor cells. In the present study, we investigated the anti-angiogenic and anti-invasive activities of wilfoside K1N. In in vivo Matrigel plug assay using C57BL/6 mice, wilfoside K1N strongly inhibited basic fibroblast growth factor-induced microvessel formation. Exposure of wilfoside K1N to human umbilical vein endothelial cells (HUVEC) suppressed in vitro tube formation at a concentration not affecting cell viability. Moreover, wilfoside K1N significantly reduced the proliferation of HUVEC and calf pulmonary artery endothelial cells. In addition, wilfoside K1N decreased in vitro invasion of HT1080 human fibrosarcoma cells, and the inhibition might be through down-regulation of activity as well as quantity of matrix metalloproteinase-9. Therefore, our present study suggests that wilfoside K1N may have a potential to have strong anti-angiogenic and anti-invasive activities both in vitro and in vivo.


Quantitative Health Risk Assessment of Indoor Radon: A Systematic Review.
Exposure to radon is a well-established cause of lung cancer in the general population. The aim of the present work is to identify and summarize the results of studies that have assessed the risk of lung cancer due to indoor radon, based on a systematic review of relevant published studies. Sixteen studies from 12 different countries met eligibility criteria. Large differences in radon concentrations were noted between and within individual countries, and variety of risk models used to estimate the attributable fraction. Calculating again the attributable fraction in each of these studies using the same model (coefficient of 16% per 100 becquerels per cubic meter (Bq/m3) derived from the European residential radon study), the new attributable fraction of these selected studies ranged from 3% to 17%. Radon remains a public health concern. Information about radon health risks is important and efforts are needed to decrease the associated health problems.


An Overview of Lenalidomide in Combination with Rituximab for the Treatment of Adult Patients with Follicular Lymphoma: The Evidence to Date.
Follicular lymphoma (FL) is an indolent (low-grade) malignancy of B cells and is among the most common hematological cancers affecting adults. Its clinical presentation, natural course, and severity are highly variable. Management of FL depends on the clinical setting; most patients require multiple lines of treatment. Chemoimmunotherapy is the standard of care for FL patients needing treatment; however, alternative treatments are limited for refractory patients or those unfit for chemoimmunotherapy. Multiple alternatives to chemoimmunotherapy for FL are being developed, with some showing significant promise. Lenalidomide combination with rituximab (LR) is among the most successful and extensively studied novel approaches. LR has been compared head-to-head in clinical trials with rituximab monotherapy and chemoimmunotherapy in the frontline and to lenalidomide or rituximab monotherapy in the relapsed or refractory setting for the treatment of FL. Initial reports of these nine trials have been published in the last decade, and their long-term data will be available in the coming years. LR offered superior efficacy to either lenalidomide or rituximab monotherapy alone. The RELEVANCE trial compared the efficacy of LR with chemoimmunotherapy among 1030 FL patients and demonstrated similar efficacy with a different side effect profile. Myelosuppression, rash, and fatigue were among the significant adverse events. Most patients treated with LR received thromboprophylaxis. This paper aims to summarize and comment on the published evidence regarding LR treatment for FL through a literature review. The clinical trials will be presented in detail, and methodological differences complicating their comparisons will be discussed.


Cystamine inhibits human immunodeficiency virus-1 replication in cord blood-derived mononuclear phagocytes and lymphocytes.
The effects of cystamine on the human immunodeficiency virus (HIV-1) expression in cord blood monocytes-derived macrophages (CBMDM) and lymphocytes were investigated. Cystamine suppressed HIV-1 expression in CBMDM and lymphocytes in a concentration-dependent fashion as determined by HIV-1 reverse transcriptase (RT) activity. This inhibitory effect of cystamine occurred with all five HIV-1 strains (both laboratory adopted and fresh isolates) tested in the study. The addition of cystamine to cultures of HIV-1 chronically infected CBMDM also suppressed 80% to 90% of RT activity in comparison with untreated controls. Cystamine also decreased HIV-1 protein expression in CBMDM as determined by indirect immunofluorescence assay. The inhibitory effects of cystamine on HIV-1 did not appear to be caused by toxicity to CBMDM or lymphocytes because there was no change in cell viability or cellular DNA synthesis as evaluated by trypan blue dye exclusion and [3H]-thymidine incorporation at doses of cystamine that inhibit the virus. HIV-1 infected CBMDM or lymphocyte cultures (without cystamine treatment) demonstrated giant syncytium formation or cytopathic effect (CPE), respectively, whereas cystamine-treated cultures lacked the giant syncytia or CPE induced by HIV-1 infection. Thus, these observations indicate that cystamine may have the potential to limit HIV-1 replication in monocytes/macrophages and lymphocytes in vivo and may represent a potentially useful compound in the treatment of pediatric HIV-1 infection and acquired immunodeficiency syndrome.


Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis.
Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total n = 1050, etanercept n = 455, infliximab n = 450), we investigated whether genotypes of eight single nucleotide polymorphisms in the region containing the TNF gene were associated with response to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint disease activity score (DAS28), baseline health assessment questionnaire score, gender and concurrent disease modifying anti-rheumatic drug treatment were used to assess association of these polymorphisms with treatment response, defined by change in DAS28 after 6 months. Analyses were performed in the entire cohort, and also stratified by anti-TNF agent. Association between DAS28 response and TNF-308 (rs1800629) genotype (P = 0.001) was detected across the whole cohort. After stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with a significantly poorer response compared with TNF-308GG in etanercept (P = 0.001, n = 7) but not infliximab (P = 0.8, n = 17) treated patients. Conversely, the GA genotype at TNF-238 (rs361525) was associated with a poorer response to infliximab (P = 0.028, n = 40), but not etanercept (P = 0.6, n = 33). Owing to the small numbers of patients in some of the genotype groups examined, our data must be regarded as preliminary and will require replication in further large cohorts of anti-TNF-treated patients. If confirmed, our findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA.


A role of Rnd1 GTPase in dendritic spine formation in hippocampal neurons.
Rho family of small GTPases are key regulators for morphological changes of neurons on the basis of reorganization of the actin cytoskeleton. Rnd1, a novel member of this family, is predominantly expressed in neurons in brain; however, the neuronal functions of Rnd1 are not known. Here we investigated the effect of Rnd1 on neuronal morphology. Northern blot analysis of Rnd1 expression in rat brain showed that Rnd1 mRNA was highly expressed during early postnatal period, the synaptogenic stage. In situ hybridization analysis at this period revealed that Rnd1 mRNA was strongly expressed in neurons, including the hippocampal pyramidal neurons. Furthermore, immunoblot analysis showed that Rnd1 protein was localized in synaptosomal membrane fraction. Ectopical overexpression of Rnd1 in cultured rat hippocampal neurons promoted the elongation of dendritic spines. On the other hand, suppression of endogenous Rnd1 level by antisense oligonucleotide of Rnd1 caused the increase in the percentage of headless protrusions accompanied by the reduction in the spine number and spine width and shortened the length of the headless protrusions. These results indicate that Rnd1 plays a role in spine formation in the developmental synaptogenic stage.


The Potential Role of miRNAs as New Biomarkers for Osteoporosis.
Osteoporosis is the most common metabolic bone disorder affecting up to 40% of postmenopausal women, characterized by a reduction in bone mass and strength leading to bone fragility and fractures. Despite the available tools for diagnosis and stratification of a fracture risk, bone loss occurs insidiously and osteoporosis is often diagnosed after the first fracture has occurred, with important health-related outcomes. Therefore, the need of markers that could efficiently diagnose bone fragility and osteoporosis is still necessary. Over the past few years, novel studies have focused on miRNAs, small noncoding RNAs that are differentially expressed in many pathological conditions, making them attractive biomarkers. To date, the role of miRNAs in bone disorders remains in great part unclear. In particular, limited and partly conflicting information is available concerning their use as potential biomarkers for osteoporosis, due to differences in patient selection, type of samples, and analytical methods. Despite these limits, concordant information about some specific miRNAs is now arising, making likely their use as additional tools to stratify the risk of osteoporosis and possibly fractures. In this review, we summarize the most relevant studies concerning circulating miRNAs differentially expressed in osteoporotic patients along with their function in bone cells and bone turnover.


Common Familial Mediterranean Fever gene mutations in a Turkish cohort.
Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder with the responsible gene of MEFV which primarily affects Jewish, Armenian, Turkish and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16 p, which encodes pyrin. In the present study, we enrolled 2,067 unrelated patients with the suspicion of FMF in Middle Anatolia between the years 2006-2009 and identified the 12 MEFV mutations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. Among the 2,067 patients, 866 (41.9%) were males and 1,201 (58.1%) were females. The mutations were homozygous in 176 (16.85%) patients, compound heterozygous in 314 (30.1%) patients, heterozygous in 546 (52.25%) patients and the other forms of mutations were found in 8 patients (0.76%). No mutation was detected in 1,023 (49.5%) patients. The most frequent mutations were M694V, M680I (G/C), E148Q and V726A. We could not find any significant differences between the two common mutations according to the gender. The high incidence of MEFV gene mutations in the Turkish population indicated that newborn screening may be discussed in the future. Because of the ethnic origin of Anatolia, larger serial analyses are necessary to investigate the rate and coexistence of these mutations.


Antimicrobial activity of resveratrol analogues.
Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity.


Clinical significance of Vitamin-D and other bone turnover markers on bone mineral density in patients with gestational diabetes mellitus.
To perform a correlation analysis of serum 25-hydroxyVitamin-D[25-OH-D], bone turnover markers (BTMs), and bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) during mid- and late pregnancy and state the significance of these factors for guiding clinical prevention and control of GDM. This study involved 100 pregnant women with singleton pregnancies who visited our obstetrics and gynecology department, Baoding First Central Hospital, during January 2019 and December 2020. All participants had received more than five prenatal checkups and were assigned to a GDM group and a normal group according to the presence of GDM during the mid-pregnancy period. Serum 25-OH-D, BMD, and bone turnover markers (BTMs) were measured to analyze the differences between the two groups and observe possible correlations among these factors. According to the examination results, GDM occurred in 31 (31%) participants, and the rest 69 (69%) were free of GDM during mid-pregnancy. No significant differences were observed between the two groups in basic clinical data and the serum levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (p>0.05), whereas the fasting blood glucose (FBG) level in the GDM group was significantly higher than in the normal group (p<0.05). The serum 25-OH-D and BMD levels in the GDM group were lower than in the normal group, whereas the bone alkaline phosphatase (BALP), osteocalcin (OC), procollagen type I propeptide (PINP), and beta-isomerized C-terminal telopeptide (β-CTx) levels in the GDM group were significantly higher than in the normal group, with the differences showing statistical significance (p<0.05, respectively). The results of Pearson's correlation analysis revealed that serum 25-OH-D was positively correlated with BMD (r =0.183, P <0.05) and negatively correlated with such BTMs as BALP, OC, PINP, and β-CTx (r =-0.255, -0.369, -0.204, -0.610; p<0.05). During mid and late pregnancy, GDM patients are prone to Vitamin-D deficiency, which has an adverse effect on bone turnover, BMD, and even the health of the mother and the development of the fetus. Therefore, routine screening for Vitamin-D deficiency is recommended throughout pregnancy.


Numerical evidence for thermally induced monopoles.
Electric charges are conserved. The same would be expected to hold for magnetic charges, yet magnetic monopoles have never been observed. It is therefore surprising that the laws of nonequilibrium thermodynamics, combined with Maxwell's equations, suggest that colloidal particles heated or cooled in certain polar or paramagnetic solvents may behave as if they carry an electric/magnetic charge. Here, we present numerical simulations that show that the field distribution around a pair of such heated/cooled colloidal particles agrees quantitatively with the theoretical predictions for a pair of oppositely charged electric or magnetic monopoles. However, in other respects, the nonequilibrium colloidal particles do not behave as monopoles: They cannot be moved by a homogeneous applied field. The numerical evidence for the monopole-like fields around heated/cooled colloidal particles is crucial because the experimental and numerical determination of forces between such colloidal particles would be complicated by the presence of other effects, such as thermophoresis.


CpG island methylation in precursors of gastrointestinal malignancies.
Gastrointestinal malignancies account for about 20% of all cancers worldwide. It is widely accepted that cancer evolves through several stepwise morphological stages such as the adenoma-carcinoma and hyperplastic polyp-serrated adenoma-carcinoma sequences in colorectal cancers, and the metaplasia-dysplasia-carcinoma sequences in esophageal and gastric cancers. The morphological progression is associated with the accumulation of multiple genetic and epigenetic events. It is now recognized that epigenetic silencing of gene expression by CpG island methylation is an important alternative mechanism of inactivating tumor suppressor genes. Inflammatory conditions of the gastrointestinal and pancreaticobiliary tracts and liver such as Barrett esophagus, Helicobacter pylori gastritis, inflammatory bowel disease and viral hepatitis, are associated with increased frequency of malignancies and CpG methylation. In addition, CpG methylation is present in aberrant crypt foci and pancreatic intraepithelial neoplasia that are considered putative precursors of colon and pancreatic carcinomas, respectively. Understanding of these early genetic and epigenetic changes allows for the discoveries of potential screening, monitoring and therapeutic strategies. Targeting of the epigenetic changes that occur before the development of frank malignancy offers a potential chemopreventive strategy.


Competence of medical students in communicating drug therapy: Value of role-play demonstrations.
This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students' competence in this skill. Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients.


The association of depressive sarcopenia and cognitive decline among the elderly: Evidence from the Survey of Health and Retirement in Europe.
The present study aimed to explore the relationship between baseline different sarcopenia statuses combined with different depression statuses and long-term cognitive functions. Finally, a total of 4289 individuals aged 50 years or older from wave 2 to wave 8 of the Survey of Health, Ageing and Retirement in Europe were included in this study. The generalized estimated equation model was used to explore the baseline effect of depression with sarcopenia on long-term cognitive function. Stratified Analyses according to gender, education, region, and family economic level were performed. Sensitivity analyses of wave 5 to wave 8 were conducted to ensure the robustness of the results. Groups of depression with non-sarcopenia (β = -0.40, 95%CI: -0.59 ~ -0.20, P < 0.001), non-depression with sarcopenia (β = -1.11, 95%CI: -1.91 ~ -0.31, P = 0.007), and depression with sarcopenia (β = -1.19, 95%CI: -1.89 ~ -0.50, P = 0.001) were inversely associated with cognition scores compared with the group of non-depression with non-sarcopenia. Stratified Analysis displayed differences in negative association of depression status with sarcopenia status and cognition. Sensitivity analyses yielded similar results. Other than numeracy, depression with sarcopenia (β = -1.81, 95%CI: -2.45 ~ -1.18, P < 0.001; β = -10.68, 95%CI: -1.05 ~ -0.31, P < 0.001; β = -0.51, 95%CI: -0.65 ~ -0.37, P < 0.001; β = -0.41, 95%CI: -0.55 ~ -0.27, P < 0.001) were inversely associated with cognitive function, orientation, words list learning test and fluency. Preliminary depressive sarcopenia appears to increase the risk of cognitive decline. There was a downward trend in total cognitive function. The effect of depression combined with sarcopenia on cognitive function may exist in differences in gender, education, region, and family economic level.


Reproducibility of retinal oxygen saturation in normal and treated glaucomatous eyes.
To measure the reproducibility of retinal oxygen saturation (SaO2) levels among treated glaucomatous eyes and normal controls in a prospective non-randomised study. Patients with perimetric glaucoma (PG) and normal controls were included. Exclusion criteria for both groups included visual acuity <20/30, unreliable visual fields, thyroidopathies, hemoglobinopathies, cardiovascular and pulmonary diseases. Retinal oximetry was performed twice consecutively on one randomly selected eye of PG and normal controls using spectrophotometric retinal oximeter (SRO; Oxymap ehf., Iceland). Four main retinal vessel pairs were analysed separately. Coefficients of variability (CoV), coefficients of repeatability (CoR) and intraclass correlation coefficients (ICCs) in arteries (a.SaO2) and veins (v.SaO2) were calculated. 23 PG (mean age 68.3±10.8 years) and 22 normal subjects (mean age 61.5±18.2 years; p=0.14) were included. The intraocular pressure and mean ocular perfusion pressure in glaucoma (14.4±4.2 mm Hg; 45.8±5.8 mm Hg) and controls (14.3±3.3 mm Hg; 45.8±6.1 mm Hg) were similar (p >0.05). In the PG group, the a.SaO2 had a CoV of 1.6%, a CoR of 4.7 and an ICC of 0.97; the v.SaO2 had a CoV of 5.9%, a CoR of 8.7 and an ICC of 0.96. In normals, the a.SaO2 had a CoV of 0.98%, a CoR of 3.3 and an ICC of 0.97; the v.SaO2 had a CoV of 4.8%, a CoR of 7.7 and an ICC of 0.93. Retinal oximetry measurements using SRO are highly reproducible in both treated glaucomatous and normal eyes.


[An attempt at the historical reconstruction of the genetic demographic structure of the Moscow population at the turn of the 20th century].
The genetic demographic structure of the Moscow population at the turn of the 20th century was studied based on the data from parish books and census records. The main sources of population gene pool replenishment were analyzed, and migration coefficients and the main parameters of the model of isolation by distance were estimated. Data on so-called quasigenetic markers (ethnicity and birthplace) were used to reveal intrapopulation heterogeneity, which facilitates the adaptation of migrants to a new ethnic and cultural environment. The spatial subdivision was analyzed with the use of GST statistics. Muscovites exhibited a considerable positive assortative mating with respect to birthplace. The results of this study provide the necessary historical perspective for predicting the current genetic demographic trends in the Moscow population. It was shown that the co-efficients of marriage migration were almost the same (0.7 < m < 0.8) in the late 19th and mid-20th centuries; however, these values were two times greater than in the late 20th century. This decrease in marriage migration was accompanied by a threefold increase in the radius of centripetal migration and a threefold decrease in the level of isolation by distance. It was determined that the increase in the ethnic and genetic diversity of the Moscow population in the 20th century had started in the 1860s.


Laboratory testing for bleeding disorders: strategic uses of high and low-yield tests.
Laboratory testing is essential for diagnosing bleeding disorders. The tests and panels that laboratories currently use for bleeding disorder evaluation are not standardized, although most offer coagulation screening tests in bleeding disorder panels. Some tests for bleeding disorders, including von Willebrand factor multimer assays and tests for rarer disorders, are not widely available. Accordingly, clinicians and laboratories need tailored strategies for evaluating common and rare bleeding disorders. Coagulation screening tests have high specificity, however, false positives and false negatives do occur among subjects evaluated for bleeding disorders and more specific tests (e.g., factor assays) are required to further assess abnormalities. Tests for defects in primary hemostasis have similar high specificity but much greater sensitivity for common bleeding disorders than coagulation screening tests. Nonetheless, extensive testing fails to establish a diagnosis in a significant number of individuals considered to have significant bleeding problems. Rare bleeding disorder investigations are important to diagnose some conditions, particularly those with delayed-onset bleeding, such as factor XIII deficiency, α2 antiplasmin deficiency, plasminogen activator inhibitor-1 deficiency, and Quebec platelet disorder. These issues need careful consideration when assessing patients for congenital and acquired bleeding problems.


The health care system has an eating disorder.
The health care system crisis has been proclaimed and analyzed so much by economists, policy analysts, politicians, business executives, and journalists that the key statistics and phrases are becoming as familiar as the lyrics of a popular song-14 percent of the GNP goes to health care, 37 million Americans lack health insurance, too many specialists and not enough primary care physicians, etc. What I have not found is a comprehensive assessment of how the health care system got so sick. The different social science specialists focus on their respective symptoms or organs, but do not propose therapies to treat the entire organism. Ilya Prigogine's Theory of Dissipative Structures (now old hat since he won the Nobel Prize in 1977) demonstrated that self-organizing systems, be they health care systems or individual patients, respond in similar ways to the demands of illness and growth. Therefore, a clinical correlation for the health care system may have more than poetic appeal. I would like to offer the following clinical analogy for what ails our health care system.


Exercise-Induced Cardioprotection via eNOS: A Putative Role of Red Blood Cell Signaling.
Moderate exercise training is a key aspect of primary and secondary prevention strategies. Shear-induced upregulation of eNOS activity and function in the vascular endothelium is considered as one of the main molecular mechanisms of exercise-induced protection against myocardial ischemia/ reperfusion (I/R) injury. It has been reported that levels of plasma nitrite, which are largely dependent on eNOS activity, were increased in healthy subjects after acute exercise, while this increase was abolished in coronary artery disease (CAD) patients. Our group and others demonstrated that RBCs contain a functional eNOS, which contributes to systemic nitrite homeostasis and to cardioprotection; moreover, expression and activity of red cell eNOS are decreased in CAD patients and significantly correlated with flow-mediated dilation, a diagnostic marker of endothelial function. Therefore, in addition to vascular eNOS, also red cell eNOS (or in more general terms NO metabolic activity of RBCs) may play a role in exercise-dependent changes of NO-bioavailability. In this review, we will focus on what is known and what is unknown about the role of RBCs in exercise-dependent cardioprotection with emphasis on RBC signaling and red cell eNOS. In detail, we will discuss the effects and molecular mechanisms of shear stress and exercise training on RBC signaling and function, review how these changes may influence blood rheology and systemic hemodynamics and highlight the potential role of red cell eNOS-mediated cardiovascular protection induced by physical activity against myocardial injury in animal and human studies and in clinical settings.


Saprophytic fungal infections and lung transplantation--revisited.
Fungal infections cause serious morbidity and death in lung transplant recipients. Some centers exclude and others will prophylactically treat patients with evidence of Aspergillus colonization. Of 126 patients undergoing lung transplantation at the University of North Carolina since January 1990, five patients have died because of invasive Aspergillus and other saprophytic fungal infections. Those cases are reviewed looking for common predisposing factors, including any evidence of prior colonization. In addition, all preoperative and postoperative culture data on all transplant recipients were retrospectively examined to define the prevalence of preoperative and postoperative Aspergillus colonization in 121 patients with and without cystic fibrosis, none of whom had development of significant fungal disease. Fifty-two percent of 65 patients with cystic fibrosis were colonized with Aspergillus before operation, and 40% after operation at some time. None had development of significant Aspergillus infections, and none received prophylactic antifungal therapy. Most of the deaths from deep-seated fungal infections have been in patients without cystic fibrosis with no evidence of preoperative colonization. These patients had evidence of severe obliterative bronchiolitis, bacterial infections, persisting cytomegalovirus disease, or other major organ failure. The rationale for excluding patients or for giving amphotericin in the perioperative period in those patients who are colonized before surgery is questioned.


Effects of long-term food reduction on the hypothalamus-pituitary-thyroid axis in male and female rats.
The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.


Nutrient and hormonal regulation of pyruvate kinase gene expression.
Mammalian pyruvate kinase (PK), a key glycolytic enzyme, has two genes named PKL and PKM, which produce the L- and R-type isoenzymes by means of alternative promoters, and the M1-and M2-types by mutually exclusive alternative splicing respectively. The expression of these genes is tissue-specific and under developmental, dietary and hormonal control. The L-type isoenzyme (L-PK) gene contains multiple regulatory elements necessary for regulation in the 5' flanking region, up to position -170. Both L-II and L-III elements are required for stimulation of L-PK gene transcription by carbohydrates such as glucose and fructose, although the L-III element is itself responsive to carbohydrates. The L-II element is also responsible for the gene regulation by polyunsaturated fatty acids. Nuclear factor-1 proteins and hepatocyte nuclear factor 4, which bind to the L-II element, may also be involved in carbohydrate and polyunsaturated fatty acid regulation of the L-PK gene respectively. However, the L-III-element-binding protein that is involved in carbohydrate regulation remains to be clarified, although involvement by an upstream stimulating factor has been proposed. Available evidence suggests that the carbohydrate signalling pathway to the L-PK gene includes a glucose metabolite, possibly glucose 6-phosphate or xylulose 5-phosphate, as well as phosphorylation and dephosphorylation mechanisms. In addition, at least five regulatory elements have been identified in the 5' flanking region of the PKM gene up to position -279. Sp1-family proteins bind to two proximal elements, but the binding of proteins to other elements have not yet been clarified. Glucose may stimulate the transcription of the PKM gene via hexosamine derivatives. Sp1 may be involved in this regulation via its dephosphorylation, although the carbohydrate response element has not been determined precisely in the PKM gene. Thus glucose stimulates transcription of the PKM gene by the mechanism which is probably different from the L-PK gene.


Modeling the optimal seasonal monoclonal antibody administration strategy for respiratory syncytial virus (RSV) prevention based on age-season specific hospitalization rate of RSV in Suzhou, China, 2016-2022.
The approval of nirsevimab brings light to reducing the heavy disease burden caused by respiratory syncytial virus (RSV). Considering the seasonality of RSV, the timing of administrating monoclonal antibody (mAb) is critical to maximize health utility. This study aimed to model and seek the optimal seasonal mAb administration strategy for preventing RSV-associated hospitalization. Age-season specific hospitalization rates for RSV-associated acute lower respiratory infection (RSV-ALRI) were estimated from a hospital-based birth cohort. Using these rates, we simulated and evaluated the effect of diverse mAb administration strategies on preventing RSV-ALRI hospitalization. Optimal strategies were selected based on their effectiveness and relative cost-effectiveness. Compared with the year-round strategy of administration mAb at birth for all children, 291 out of the 854 candidate strategies, featuring diverse administration timing and age thresholds, demonstrated a greater number of averted RSV-ALRI hospitalizations and a lower number needed to treat (NNT). The NNT represents the number of mAb doses needed to prevent one case of RSV-ALRI hospitalization. Among the 291 strategies, administration mAb to children born in July-January or August-January at birth and administrating to the remaining <12 months old children in September, exhibited the highest increase in averted RSV-ALRI hospitalizations than the year-round strategy, with a magnitude of 23 %, while also achieve an 18 % reduction in NNT. Administrating monoclonal antibodies to children born in July to January at birth, and administrating to the remaining <1-year-old children in September or October would be the optimal seasonal mAb administration strategy for children in Suzhou, China.


Novel Compound Heterozygous Variants in TBCD Gene Associated with Infantile Neurodegenerative Encephalopathy.
Mutations in tubulin-specific chaperon D (TBCD), the gene encoding one of the co-chaperons required for the assembly and disassembly of the α/β-tubulin heterodimers, have been reported to cause perturbed microtubule dynamics, resulting in debilitating early-onset progressive neurodegenerative disorder. Here, we identified two novel TBCD variants, c.1340C>T (p.Ala447Val), and c.817+2T>C, presented as compound heterozygotes in two affected siblings born to unaffected carrier parents. Clinical features included early-onset neurodegeneration, failure to thrive, respiratory failure, hypotonia, muscle weakness and atrophy and seizures. We established the genotype-phenotype relationship of these TBCD pathogenic variants and provided insight into the protein structural alteration that may contribute to this chaperone-associated tubulinopathy.


Role of bacterial cellulose fibrils in Agrobacterium tumefaciens infection.
During the attachment of Agrobacterium tumefaciens to carrot tissue culture cells, the bacteria synthesize cellulose fibrils. We examined the role of these cellulose fibrils in the attachment process by determining the properties of bacterial mutants unable to synthesize cellulose. Such cellulose-minus bacteria attached to the carrot cell surface, but, in contrast to the parent strain, with which larger clusters of bacteria were seen on the plant cell, cellulose-minus mutant bacteria were attached individually to the plant cell surface. The wild-type bacteria became surrounded by fibrils within 2 h after attachment. No fibrils were seen with the cellulose-minus mutants. Prolonged incubation of wild-type A. tumefaciens with carrot cells resulted in the formation of large aggregates of bacteria, bacterial fibrils, and carrot cells. No such aggregates were formed after the incubation of carrot cells with cellulose-minus A. tumefaciens. The absence of cellulose fibrils also caused an alteration in the kinetics of bacterial attachment to carrot cells. Cellulose synthesis was not required for bacterial virulence; the cellulose-minus mutants were all virulent. However, the ability of the parent bacterial strain to produce tumors was unaffected by washing the inoculation site with water, whereas the ability of the cellulose-minus mutants to form tumors was much reduced by washing the inoculation site with water. Thus, a major role of the cellulose fibrils synthesized by A. tumefaciens appears to be anchoring the bacteria to the host cells, thereby aiding the production of tumors.


Natural vs synthetic auxin: studies on the interactions between plant hormones and biological membrane lipids.
Analysis of the interactions between two representatives of plant hormones: synthetic (1-naphthaleneacetic acid, NAA) as well as natural (indole-3-acetic acid, IAA) and phospholipids occurring in biological membrane of both plant and animal cells was the subject of present studies. The aim of undertaken experiments was to elucidate the problem of direct influence of these plant growth regulators on phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in monolayers at the air/water solution interface. The studied phospholipids differ not only as regards the structure of polar head-groups but also in the length of hydrophobic chains as well as their saturation degree. These differences result also in the main properties and functions of these phospholipids in biomembranes. The analysis of the results was based on the characteristics of the surface pressure (π)--area (A) isotherms registered for monolayers spread on the subphase containing plant hormone and as a reference on the surface of pure water. Moreover, as a complementary technique, Brewster angle microscopy was applied for the direct visualization of the investigated surface films. The obtained results revealed that auxins effectively influence phospholipids monolayers, regardless of the lipid structure, at the concentration of 10(-4)M. It was found that for this concentration, the influence of auxins was visibly larger in the case of PCs as compared to PEs. On the other hand, in the case of auxins solution of ≤ 10(-5)M, the observed trend was opposite. Generally, our studies showed that the natural plant hormone (IAA) interacts with the investigated lipid monolayers stronger than its synthetic derivative (NAA). The reason of these differences connects with the steric properties of both auxins; namely, the naphthalene ring of NAA molecule occupies larger space than the indole system of IAA. Therefore molecules of the latter compound penetrate easier into the region of phospholipids׳ polar head-groups. Moreover, the NH group of the indole moiety is capable of hydrogen bond formation with the acceptor groups in the polar fragment of lipid molecules. We proved also that among the investigated phospholipids, the highest susceptibility toward auxin influence show these lipids, for which during compression, surface film increases the degree of condensation.


Commissioning and initial experience with the first clinical gantry-mounted proton therapy system.
The purpose of this study is to describe the comprehensive commissioning process and initial clinical experience of the Mevion S250 proton therapy system, a gantry-mounted, single-room proton therapy platform clinically implemented in the S. Lee Kling Proton Therapy Center at Barnes-Jewish Hospital in St. Louis, MO, USA. The Mevion S250 system integrates a compact synchrocyclotron with a C-inner gantry, an image guidance system and a 6D robotic couch into a beam delivery platform. We present our commissioning process and initial clinical experience, including i) CT calibration; ii) beam data acquisition and machine characteristics; iii) dosimetric commissioning of the treatment planning system; iv) validation through the Imaging and Radiation Oncology Core credentialing process, including irradiations on the spine, prostate, brain, and lung phantoms; v) evaluation of localization accuracy of the image guidance system; and vi) initial clinical experience. Clinically, the system operates well and has provided an excellent platform for the treatment of diseases with protons.


Mitochondrial and chloroplastic targeting signals of NADP+-dependent isocitrate dehydrogenase.
Many mitochondrial and chloroplast proteins are encoded in the nucleus and subsequently imported into the organelles via active protein transport systems. While usually highly specific, some proteins are dual-targeted to both organelles. In tobacco (Nicotiana tabacum L.), the cDNA encoding the mitochondrial isoform of NADP+-dependent isocitrate dehydrogenase (NADP+-ICDH) contains two translational ATG start sites, suggesting the possibility of tandem targeting signals. In this work, the putative mitochondrial and chloroplastic targeting signals from NADP+-ICDH were fused to a yellow fluorescent protein (YFP) reporter to generate a series of constructs and introduced into tobacco leaves by Agrobacterium-mediated transient transformation. The subsequent sub-cellular locations of the ICDH:YFP fusion proteins were then examined using confocal microscopy. Constructs predicted to be targeted to the chloroplast all localized to the chloroplast. However, this was not the case for all of the constructs that were predicted to be mitochondrial targeted. Although some constructs localized to mitochondria as expected, others appeared to be chloroplast localized. This was attributed to an additional 50 amino acid residues of the mature NADP+-ICDH protein that were present in those constructs, generated from either 'Xanthi' or 'Petit Havana' cultivars of tobacco. The results of this study raise interesting questions regarding the targeting and processing of organellar isoforms of NADP+-ICDH.


Occurrence, Chronicity and Intensity of Itch in a Clinical Consecutive Sample of Patients with Skin Diseases: A Multi-centre Study in 13 European Countries.
Itch is an unpleasant symptom, affecting many dermatological patients. Studies investigating the occurrence and intensity of itch in dermatological patients often focus on a single skin disease and omit a control group with healthy skin. The aim of this multi-centre study was to assess the occurrence, chronicity and intensity (visual analogue scale 0-10) of itch in patients with different skin diseases and healthy-skin controls. Out of 3,530 dermatological patients, 54.3% reported itch (mean ± standard deviation itch intensity 5.5 ± 2.5), while out of 1,094 healthy-skin controls 8% had itch (3.6 ± 2.3). Chronic itch was reported by 36.9% of the patients and 4.7% of the healthy-skin controls. Itch was most frequent (occurrence rates higher than 80%) in patients with unclassified pruritus, prurigo and related conditions, atopic dermatitis and hand eczema. However, many patients with psychodermatological conditions and naevi also reported itch (occurrence rates higher than 19%).


Effects of spring-loaded posterior bite-block appliance on masticatory muscles.
The effects of spring-loaded posterior bite-blocks on masticatory muscles were investigated to evaluate the correlation between masticatory muscles and craniofacial form in long-faced children. The appliance was used in 10 subjects (6 girls and 4 boys) with a chronological mean age of 10.40 +/- 1.12 years for the treatment of skeletal anterior open bite. Electromyographic activity of the anterior and posterior temporal and masseter muscles was recorded before and after treatment during postural position, maximal biting, chewing, swallowing, postural position with the appliance in the mouth, and maximal biting with the appliance in the mouth. After treatment, increases in SNB and overbite (P <.05, P <.001, respectively) and decreases in ANB, SNGoAr, and overjet parameters were found to be statistically significant (P <.05, P <.01). When the measurements related to muscle activity were examined, increases in anterior temporal postural (P <.05), anterior temporal chewing (P <.01), masseter chewing (P <.05), posterior temporal chewing (P <. 05), and masseter swallowing (P <.01) were found to be statistically significant. A positive correlation was found between ANB and anterior temporal postural and a negative correlation between SNGoAr and masseter swallowing. The increase in muscle activities was considered to occur as a result of the appliance used.


High concentrations of retinoids induce differentiation and late apoptosis in pancreatic cancer cells in vitro.
Our previous investigations showed that retinoids, at specific concentrations, can inhibit cell proliferation. In this investigation, we hypothesize that high concentrations of retinoids can induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. To test our hypothesis, retinoid-induced differentiation was assessed: (1) phenotypically by light and electron microscopy and (2) biochemically by measuring carbonic anhydrase, aerobic metabolic and mucin producing activities. Modulation of transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) autocrine pathways were utilized as mechanistic and differentiation markers. The extensive differentiation-indicative phenotypic changes correlated with several folds increase in the aerobic metabolism (MTT reduction and Mitochondrial mass), carbonic anhydrase activity and mucin production. There was a marked increase in TGF-beta (Bioassay and ELISA) and TGF-beta (RIA) secretion. EGF receptor density (Receptor binding assay) was reduced by 50% within six hours and was reflected on abolishment of EGFR ligand-induced proliferation. Cotreatment with the RAR-alpha antagonist, Ro41-5253 or pan-TGF-beta neutralizing antibody abolished the phenotypic and antiproliferative effects of all-trans retinoic acid. Apoptosis (TUNEL assay) was undetectable after three days of treatment with the maximum concentration used. However, apoptosis was extensively induced after six days of treatment. High concentrations of retinoids were able to induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. The clinical ramifications of these observations await further investigations.


Measuring the length distribution of self-assembled lipid nanotubes by orientation control with a high-frequency alternating current electric field in aqueous solutions.
The present work addresses the length distribution of self-assembled lipid nanotubes (LNTs) by controlling the orientation of the LNTs using an alternating current (ac) electric field in aqueous solutions. The effect of the ac field on the orientation and rotation of individual LNTs was examined to evaluate the optimum orientation frequency by visualizing the individual LNTs in real time. By using the high-frequency ac field, we have successfully measured the length distribution for two different types of LNTs and have quantitatively analyzed the maximum occurrences of the length distribution as well as the extension of the longer length region.


The diagnostic value of the premature ejaculation diagnostic tool and its association with intravaginal ejaculatory latency time.
Premature ejaculation (PE) is the most prevalent male ejaculation disorder. The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the DSM-IV-TR criteria in diagnostic PE. To evaluate the diagnostic value of the PEDT and its association with intravaginal ejaculatory latency time (IELT). (i) Korean validation of PEDT: data was collected from men interviewed by one of the two clinical experts, who made a diagnostic of present or absence of PE, using DSM-IV-TR criteria. A total of 103 patients with PE and 100 men without PE were enrolled into the study and requested to complete the PEDT; and (ii) The correlation between IELT and PEDT: 200 participants were enrolled and each participant was asked to make out PEDT. All participants were requested to measure IELT. Validity and reliability of the PEDT and its association with IELT. The geometric mean IELT of the PE group was 115.37 ± 78.14 seconds. The number of men reporting IELTs of <1, 1 to ≤ 2, and >2 minutes were 28 (28.6%), 29 (29.6%), and 41 (41.8%), respectively. The Cronbach's alpha score was calculated as 0.93, showing adequate internal consistency. The test-retest correlation coefficients of each item were higher than 0.72 and the correlation coefficients of the total score was 0.88. (P < 0.001) Sensitivity and specificity analyses suggested a score of ≤ 8 indicated no PE, 9 and 10 probable PE, and ≥ 11 PE. The PEDT total score and IELT showed an adequate negative correlation. (ρ = -0.77, P < 0.0001) also, the PEDT total score of the PE subgroup (IELT ≤ 2 minutes) and IELT showed a negative correlation. (ρ = -0.6, P < 0.0001) The PEDT was highly effective in detecting the presence of PE. The result of our study supports its validity as a diagnostic tool in the clinical setting.


Cardiovascular effects of doxorubicin-induced toxicity in the intact Lou/M Wsl rat and in isolated heart preparations.
Hemodynamic effects were followed for 25 days in conscious nontumor bearing Lou/M Wsl rats during i.v. administration of doxorubicin (DXR) (1 mg/kg) on 5 consecutive days and then weekly. At day 24 cardiac output was significantly reduced in the DXR-treated group (cumulative dose of 7 mg/kg) in comparison with a saline-treated group, suggesting a reduction in myocardial performance. Urethane anesthesia at day 25 depressed cardiac output in control rats whereas this variable was not influenced in DXR-treated rats. Furthermore, blood pressure was significantly higher within DXR-treated rats, suggesting the presence of compensatory mechanisms. Separate experiments 25 days after the first DXR administration (cumulative dose of 7 mg/kg) demonstrated that the inotropic response toward dobutamine or norepinephrine as well as the vasoconstrictor response toward norepinephrine were impaired profoundly, suggesting compensatory mechanisms were functioning within the DXR-treated rats around day 25. In the isolated and perfused rat heart no changes in myocardial contraction under either basal or inotropic stimulatory conditions were observed 24 days after DXR treatment, indicating extracardiac phenomena have to contribute to a reduction in cardiac output and the occurrence of counter regulation mechanisms as observed in the in vivo experiments. However, after a cumulative dose of 11 mg/kg (at day 52), contraction function appeared to be disturbed upon contractility demand by dobutamine in the isolated heart. This observation supports the histological evidence of cardiomyopathy occurring at that time.(ABSTRACT TRUNCATED AT 250 WORDS)


Neighborhood × Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) interactions for substance use from ages 10 to 24 years using a harmonized data set of African American children.
This study investigated the influences of neighborhood factors (residential stability and neighborhood disadvantage) and variants of the serotonin transporter linked polymorphic region (5-HTTLPR) genotype on the development of substance use among African American children aged 10-24 years. To accomplish this, a harmonized data set of five longitudinal studies was created via pooling overlapping age cohorts to establish a database with 2,689 children and 12,474 data points to span ages 10-24 years. A description of steps used in the development of the harmonized data set is provided, including how issues such as the measurement equivalence of constructs were addressed. A sequence of multilevel models was specified to evaluate Gene × Environment effects on growth of substance use across time. Findings indicated that residential instability was associated with higher levels and a steeper gradient of growth in substance use across time. The inclusion of the 5-HTTLPR genotype provided greater precision to the relationships in that higher residential instability, in conjunction with the risk variant of 5-HTTLPR (i.e., the short allele), was associated with the highest level and steepest gradient of growth in substance use across ages 10-24 years. The findings demonstrated how the creation of a harmonized data set increased statistical power to test Gene × Environment interactions for an under studied sample.


Radiofrequency ablation for the treatment of radiation proctitis.
The main endoscopic therapy for radiation proctitis is argon plasma coagulation (APC); however treatment is not always successful. Radiofrequency ablation (RFA) is a possible treatment for radiation proctitis but data are scarce. The aim of this study was to report on the safety and efficacy of RFA in the treatment of radiation proctitis. This study was an open-label, retrospective, multicenter study of patients with chronic hemorrhagic radiation proctitis who were treated with RFA. Data included a three-item symptom score, the number of packed red blood cell transfusions, the lowest hemoglobin concentration, and complications, during the 6 months prior to and after RFA. Clinical success was defined as a decrease in the symptom score. Biological success was defined as an increase in the hemoglobin rate with equal or decreased number of transfusions required. A total of 17 patients underwent a median of 2 RFA sessions (range 1 - 4), without perioperative complications. Symptom scores decreased in 16 patients (clinical success 94 %), from a mean score of 3.6 (median 4) to 1.4 (median 1) (P < 0.01). Two patients developed rectal ulceration, with no local symptoms. During the 6 months after RFA, hemoglobin concentration increased in all 17 patients (from mean 8.3 ± 2.8 g/dL [median 7.5] to 11.3 ± 2.2 g/dL [median 11.0]; P < 0.01). Among 13 patients who were transfusion dependent prior to RFA (mean 7.2 ± 7.7 transfusions [median 4]), 9 patients (69 %) were weaned off transfusions after RFA. A significant increase in the hemoglobin level was observed in this subgroup of patients (from mean 7.2 ± 1.4 g/dL [median 7.3] to 10.7 ± 1.5 g/dL [median 10.5]; P < 0.001). Biological success was 100 %. RFA seems to significantly decrease clinical symptoms and increase the hemoglobin concentration, thus reducing the need for transfusions.


In-situ polymerization at the interfaces of micelles: a "grafting from" method to prepare micelles with mixed coronal chains.
Herein we describe a new strategy for producing micelles with mixed coronal chains. This method involves attachment of an atom transfer radical polymerization (ATRP) initiator at the interface of a micelle and preparation of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes at the interface by a "grafting from" method. Poly(ethylene glycol)- block-polystyrene (PEG- b-PS) diblock copolymer was achieved by ATRP. After the sulfonation reaction PS blocks were partly sulfonated. In aqueous solution at low pH the sulfonated block copolymer self-assembled into micelles with PS cores and PEG coronae and sodium 4-styrenesulfonate groups were distributed at the interfaces of the micelles. An ATRP initiator consisting of a quaternary ammonium salt moiety and a 2-bromo-2-methyl propionate moiety was ion exchanged onto the interface of the micelle. ATRP of DMAEMA was initiated at the interface, and micelles with PEG/PDMAEMA mixed coronal chains were prepared by ATRP. The structures of the micelles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential measurements. The size and morphology of the micelles were controlled by pH in aqueous solution. At high pH, PDMAEMA brushes collapse, forming nanodomains on the surface of the micelles. PDMAEMA brushes in the coronae of the micelles could be used as a template for preparation of gold nanoparticles.


Dorsal Augmentation using Alloplastic Implants.
Dorsal augmentation is an essential procedure not only for Asians, who generally have indistinct and poorly developed nasal bridges, but also for Africans and Caucasians, who have similar dorsal deficiencies. There is no single ideal implant or graft for dorsal augmentation. Dorsal augmentation with autologous materials is considered ideal by many surgeons. However, harvesting autologous material is associated with donor-site complications, and these materials are difficult to handle and shape. Despite concerns over complications such as infection, extrusion, and deviation, alloplastic implant materials such as silicone or Gore-Tex have a critically important role in typical cosmetic dorsal augmentation due to their ease of use in producing a cosmetically appealing outcome and evading donor-site complications. A thorough understanding of the shape of an aesthetically pleasing nose, appropriate surgical technique, and proper management methods for complications are the mainstay for the success of dorsal augmentation using alloplastic implants.


CD8+ T-cells count in acute myocardial infarction in HIV disease in a predominantly male cohort.
Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR=1.82, P<0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts<200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.


Auditory thalamus, dorsal hippocampus, basolateral amygdala, and perirhinal cortex role in the consolidation of conditioned freezing to context and to acoustic conditioned stimulus in the rat.
On the basis of previous experimental evidence, it is known that the auditory thalamus (AT), the dorsal hippocampus (DH), the basolateral amygdala (BLA), and the perirhinal cortex (PC) are involved in the mnemonic processing of conditioned freezing. In particular, BLA and PC appear to be involved both in conditioned stimulus (CS) and context conditioned freezing. Through AT, the auditory CS is sent to other sites, whereas DH is involved in context conditioning. Nevertheless, the existing evidence does not make it possible to assess AT, DH, BLA, and PC involvement during the consolidation phase of conditioned freezing. To address this question, fully reversible tetrodotoxin (TTX) inactivation was performed on adult male Wistar rats having undergone CS and context fear training. Anesthetized animals were injected stereotaxically with TTX (either 5 or 10 ng in 0.5 or 1.0 microliter of saline, according to site dimensions) at increasing post-acquisition delays. Context and CS freezing durations were measured during retention testing, always performed 48 and 72 hr after TTX administration. The results showed that AT inactivation does not disrupt consolidation of either contextual or auditory fear memories. In contrast, inactivation of the other three structures disrupted consolidation. For the DH, this disruption was specific to contextual cues and only occurred when inactivation was performed early (up to 1.5 hr) after training. The BLA and PC were shown to be involved in the consolidation of both contextual and auditory fear. Their involvement persisted for longer periods of time (2d for BLA and 8 d for PC). These findings provide information to build a temporal profile for the post-training processing of fear memories in structures known to be important for this form of learning. The results are discussed in relation to previous studies on conditioned freezing and other aversive conditioned response neural correlates.


Evaluation of aortic distensibility in patients with mitral valve prolapse using echocardiography and applanation tonometry.
Mitral valve prolapse (MVP) is a heart valve anomaly that affects a considerable segment of the population. Studies of patients with isolated MVP have shown that aortic distensibility decreased as the aortic diameter increased. The aim of this study was to compare evaluations of aortic distensibility in MVP patients using both applanation tonometry and the conventional echocardiographic examination. A total of 36 consecutive patients with MVP (16 male and 20 female) and 23 healthy controls (11 male and 12 female) were included in this study. The difference in aortic diameter and distensibility was examined using echocardiography and pulse wave velocity (PWV) was measured with applanation tonometry. According to the echocardiographic measurements, the aortic distensibility was lower in the MVP patients than in the control group (6.2±4.0 cm².dyn⁻¹.10⁻⁶ vs. 10.0±5.2 cm². dyn⁻¹.10⁻⁶; p=0.02). The PWV measured with applanation tonometry was significantly higher in the MVP patients than in the control group (9.0±2.4 m/s vs. 7.2±1.4 m/s; p=0.006). The results of this study showed that aortic distensibility was reduced in patients with isolated MVP compared with a healthy control group. There was a moderate negative correlation between the results of both methods.


Stereoselective synthesis of optically active bicyclic beta-lactam carboxylic acids that target pilus biogenesis in pathogenic bacteria.
Optically active bicyclic beta-lactams were synthesized, starting from 2-H-delta 2-thiazolines and Meldrum's acid derivatives. Several methods to accomplish an ester hydrolysis without damaging the beta-lactam framework were investigated. A rapid CsOH saponification of the beta-lactam methyl esters was developed and protonation of the Cs-carboxylates by Amberlite (IR-120 H+) afforded a series of bicyclic beta-lactam carboxylic acids. Moreover, a convenient method for the synthesis of 2-H-delta 2-thiazolinecarboxylic acid methyl ester 2 was developed. Bicyclic beta-lactam carboxylic acids 7a-g and aldehydes 4a-d were screened for their affinity to the bacterial periplasmic chaperone PapD using a surface plasmon resonance technique. beta-Lactams substituted with large acyl substitutents showed better binding to the chaperone than the native C-terminal peptide PapG 8, demonstrating that bicyclic beta-lactams constitute a new class of potential bacterial chaperone inhibitors.


Effects of ethanol on tonic GABA currents in cerebellar granule cells and mammalian cells recombinantly expressing GABA(A) receptors.
The effects of ethanol on the GABA(A) receptors, which are regarded as one of the most important target sites of ethanol, are very controversial, ranging from potentiation to no effect. The delta subunit-containing GABA(A) receptors expressed in Xenopus oocytes were recently reported to be potently augmented by ethanol. We performed patch-clamp experiments using the cerebellar granule cells and mammalian cells expressing recombinant GABA(A) receptors. In granule cells, the sensitivity to GABA increased from 7 to 11 days in vitro. Furosemide, an antagonist of alpha6-containing GABA(A) receptors, inhibited GABA-induced currents more potently at 11 to 14 days than at 7 days. Ethanol at 30 mM had either no effect or an inhibitory effect on currents induced by low concentrations of GABA in granule cells. On alpha4beta2delta, alpha6beta2delta, or alpha6beta3deltaGABA(A) receptors expressed in Chinese hamster ovary cells, ethanol at 10, 30, and 100 mM had either no effect or an inhibitory effect on GABA currents. Ethanol inhibition of GABA(A) receptor was observed in all of the subunit combinations examined. In contrast, the perforated patch-clamp method to record the GABA currents revealed ethanol effects on the alpha6beta2delta subunits ranging from slight potentiation to slight inhibition. Ethanol seems to exert a dual action on the GABA(A) receptors and the potentiating action may depend on intracellular milieu. Thus, the differences between the GABA(A) receptors expressed in mammalian host cells and those in Xenopus oocytes in the response to ethanol might be due to changes in intracellular components under patch-clamp conditions.


Effectiveness of TruScreen for detecting CIN2+ in women with ThinPrep cytologic test results indicating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.
Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.


Denaturing gradient gel electrophoresis analysis of bacterial communities associated with failed endodontic treatment.
A great deal of evidence indicates that persistent infections of the root canal of human teeth play an important role in the failure of the root canal treatment. The present study was undertaken to apply the PCR-DGGE fingerprinting approach to examine the structure of the bacterial population infecting previously treated root canals of humans associated with persistent periradicular lesions. Samples were taken from 14 filled root canals, DNA was extracted, and part of the 16S rDNA of all bacteria was amplified by PCR and separated by DGGE, generating banding patterns representative of the community structure. Species-specific PCR for the detection of Enterococcus faecalis was also performed. The mean number of bands detected in the 16S rDNA community profiles was about 6, ranging from 1 to 26 bands. Each sample showed a unique structure of the microbial community. The species-specific PCR assay revealed the presence of E. faecalis in 10 of 14 samples, but DGGE analysis revealed it was not the dominant species. Results revealed that the intraradicular bacterial community associated with failed endodontic treatment significantly varied in composition from teeth to teeth. Persistent intraradicular infections were present in all root-filled teeth.


The frequency of occurrence of fish-shaped red blood cells in different haematologic disorders.
Red blood cells (RBC) resembling the silhouette of a fish are rarely observed in peripheral blood (PB) smears. In this study, we determined the frequency of occurrence of fish-shaped RBC in different haematologic diseases. We examined PB smears of patients with iron deficiency anaemia (IDA) (n=23), β-thalassaemia minor (BTM) (n=30), sickle cell disease (SCD) (n=7), autoimmune haemolytic anaemia (AIHA) (n=13), microangiopathic haemolytic anaemia (MAHA) (n=11), hereditary sphaerocytosis (HS) (n=4), hereditary elliptocytosis (HE) (n=3), vitamin B12 and folate deficiency (n=15), anaemia in liver disease (LD) (n=17), myelodysplastic syndrome (MDS) (n=15), acute myeloid leukaemia (AML) (n=29), chronic myeloid leukaemia (CML) (n=18), primary myelofibrosis (PMF) (n=12), chronic myelo-monocytic leukaemia (CMML) (n=15) and 21 healthy controls by light microscopy for the occurrence of fish-shaped erythrocytes. The fish-shaped RBC were counted as cells per 20 high-power fields (HPF) at 1000-fold magnification, and slides containing ≥1 fish-shaped RBC/20 HPF were regarded as positive. Fish-shaped RBC were significantly found in HE, iron deficiency, vitamin B12/folate deficiency, LD and PMF. The highest numbers of fish-shaped RBC were seen in HE and vitamin B12/folate deficiency. In patients with BTM, MDS, AML and CMML, this RBC anomaly was only occasionally observed. Furthermore, a statistically significant negative correlation of haemoglobin with the occurrence of fish-shaped RBC was apparent (p<0.014). Our data show that the occurrence of fish-shaped RBC is suggestive of a pathologic condition, especially IDA, HE, vitamin B12 or folate deficiency, primary mylofibrosis or LD, and is significantly associated with severity of anaemia.


Facial appearance affects science communication.
First impressions based on facial appearance predict many important social outcomes. We investigated whether such impressions also influence the communication of scientific findings to lay audiences, a process that shapes public beliefs, opinion, and policy. First, we investigated the traits that engender interest in a scientist's work, and those that create the impression of a "good scientist" who does high-quality research. Apparent competence and morality were positively related to both interest and quality judgments, whereas attractiveness boosted interest but decreased perceived quality. Next, we had members of the public choose real science news stories to read or watch and found that people were more likely to choose items that were paired with "interesting-looking" scientists, especially when selecting video-based communications. Finally, we had people read real science news items and found that the research was judged to be of higher quality when paired with researchers who look like "good scientists." Our findings offer insights into the social psychology of science, and indicate a source of bias in the dissemination of scientific findings to broader society.


Bonding and wear characteristics of a tri-n-butylborane initiated adhesive resin filled with pre-polymerized composite particles.
This study evaluated the wear characteristics and bonding to silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy of an acrylic resin that was filled with pre-polymerized composite particles and initiated with tri-n-butylborane (TBB) derivative (Bondfill). Three methyl methacrylate (MMA)-based resins (Bondfill, Super-Bond, and Multi-Bond II) and a microfilled composite restorative material (Metafil C) were assessed. Disk specimens were cast from the alloy and were air-abraded with alumina. The disks were bonded with nine bonding systems selected from two priming and three luting agents. Shear bond strengths were measured before and after thermocycling. Bond strength varied from 2.2 MPa to 28.2 MPa. Three systems based on thione primers (Metaltite and V-Primer) and TBB-initiated resins (Bondfill and Super-Bond) had the highest bond strength after thermocycling (15.9-20.4 MPa). The toothbrush-dentifrice abrasion test showed that the Metafil C material was the most wear-resistant, followed by Bondfill and Super-Bond. In conclusion, Bondfill resin is an alternative to Super-Bond resin for luting metallic restorations and for restoring tooth defects. However, care is required in selecting appropriate clinical cases.


Simultaneous determination of pesticides from soils: a comparison between QuEChERS extraction and Dutch mini-Luke extraction methods.
The expanding nature of the agricultural sector has fuelled the intensification of plant protection products usage, including pesticides. These pesticides may persist in soils, necessitating their accurate determination in a variety of soil types. However, due to their complex nature, the effective extraction of pesticide residues from soil matrices can present challenges to pesticide detection and quantification. This research compared two well-known extraction methods, QuEChERS and Dutch mini-Luke, by assessing their specificity, sensitivity, accuracy, precision and reproducibility in extracting seven distinct pesticides with a range of chemico-physical characteristics from Irish soils. The HPLC-UV conditions were optimised to separate the seven pesticides, and it was shown that both extraction methods successfully extracted neonicotinoids with recovery values ranging between 85 and 115%. Fluroxypyr and prothioconazole could not be efficiently extracted using QuEChERS, however, the recovery values of both the analytes ranged between 59 and 117% using Dutch mini-Luke. Furthermore, with the exception of prothioconazole using Dutch mini-Luke, both extraction methods resulted in reproducibility and precision values below or equal to 20%. Lastly, Dutch mini-Luke is noted to have a lower matrix effect than QuEChERS, except for prothioconazole. The comparison results showed that Dutch mini-Luke resulted in superior method sensitivity, better recovery, and lower matrix effect towards most investigated analytes and was the only extraction technique that successfully extracted all pesticides analysed in soil matrices.


Automatic segmentation of diatom images for classification.
A general framework for automatic segmentation of diatom images is presented. This segmentation is a critical first step in contour-based methods for automatic identification of diatoms by computerized image analysis. We review existing results, adapt popular segmentation methods to this difficult problem, and finally develop a method that substantially improves existing results. This method is based on the watershed segmentation from mathematical morphology, and belongs to the class of hybrid segmentation techniques. The novelty of the method is the use of connected operators for the computation and selection of markers, a critical ingredient in the watershed method to avoid over-segmentation. All methods considered were used to extract binary contours from a large database of diatom images, and the quality of the contours was evaluated both visually and based on identification performance.


Estimating occupancy of Chinese pangolin (Manis pentadactyla) in a protected and non-protected area of Nepal.
Chinese pangolin is the world's most heavily trafficked small mammal for luxury food and traditional medicine. Although their populations are declining worldwide, it is difficult to monitor their population status because of its rarity and nocturnal behavior. We used site occupancy (presence/absence) sampling of pangolin sign (i.e., active burrows) in a protected (Gaurishankar Conservation Area) and non-protected area (Ramechhap District) of central Nepal with multiple environmental covariates to understand factors that may influence occupancy of Chinese pangolin. The average Chinese pangolin occupancy and detection probabilities were Ψ ^ ± SE = 0.77 ± 0.08; p ^ ± SE = 0.27 ± 0.05, respectively. The detection probabilities of Chinese pangolin were higher in PA ( p ^ ± SE = 0.33 ± 0.03) than compared to non-PA ( p ^ ± SE = 0.25 ± 0.04). The most important covariates for Chinese pangolin detectability were red soil (97%), food source (97.6%), distance to road (97.9%), and protected area (97%) and with respect to occupancy was elevation (97.9%). We recommended use of remote cameras and potentially GPS collar surveys to further investigate habitat use and site occupancy at regular intervals to provide more reliable conservation assessments.


Psychotherapists' duties to third parties: Ramona and beyond.
This paper explores the implications for psychotherapy of a series of court cases involving suspected childhood sexual abuse that have raised the question of when psychiatrists and other psychotherapists can be sued by third parties for their behavior in therapy. The authors begin by considering traditional legal approaches that until now, with few exceptions, granted only patients the right to sue caregivers for negligence. Then they turn to Ramona v. Ramona, the most publicized of a new line of cases, in which the California courts allowed a father accused of abusing his daughter to sue his daughter's therapists. The rationale for the abandonment of the previous restrictions on liability in Ramona was that since the father was a "direct victim" of the therapists' negligence, traditional limitations on the therapists' duties toward him should not apply. Related cases have used similar logic. Inherently difficult for the courts to apply, the direct victim standard would leave therapists unclear as to how to avoid duties to third parties, other than by refusing to treat patients with family members who may be potential litigants. Moreover, aggrieved third parties essentially would have the power to bring effective treatment to a halt by filing suit or threatening to do so. Although concern about therapeutic practices related to memories of childhood abuse may be warranted, abandonment of traditional rules against suits by nonpatients would be ill-advised. In the meantime, therapists can take steps to lessen the probability of their becoming involved in such litigation.


Aspects of structural landscape of human islet amyloid polypeptide.
The human islet amyloid polypeptide (hIAPP) co-operates with insulin to maintain glycemic balance. It also constitutes the amyloid plaques that aggregate in the pancreas of type-II diabetic patients. We have performed extensive in silico investigations to analyse the structural landscape of monomeric hIAPP, which is presumed to be intrinsically disordered. For this, we construct from first principles a highly predictive energy function that describes a monomeric hIAPP observed in a nuclear magnetic resonance experiment, as a local energy minimum. We subject our theoretical model of hIAPP to repeated heating and cooling simulations, back and forth between a high temperature regime where the conformation resembles a random walker and a low temperature limit where no thermal motions prevail. We find that the final low temperature conformations display a high level of degeneracy, in a manner which is fully in line with the presumed intrinsically disordered character of hIAPP. In particular, we identify an isolated family of α-helical conformations that might cause the transition to amyloidosis, by nucleation.


Hemorrhage Risk in Moyamoya Disease with Fetal-Type Posterior Cerebral Artery: A Propensity Score-Matched Analysis.
Patients with moyamoya disease (MMD) and fetal-type posterior cerebral arteries have not been thoroughly investigated as yet. We focused on the risk of intracranial hemorrhage in patients with MMD and fetal-type posterior cerebral arteries. We reviewed 2422 patients with MMD diagnosed at the Neurosurgical Department of Beijing Tiantan Hospital between May 2009 and December 2020. We classified patients into 2 groups according to whether they had a fetal-type posterior cerebral artery. After 1:1 propensity score matching, hemorrhagic tendency and Suzuki stage were compared between patients with a fetal-type posterior cerebral artery (group I) and patients without a fetal-type posterior cerebral artery (group II). In total, 2415 patients were included in this study; 181 had fetal-type posterior cerebral arteries. Hemorrhagic events were more frequently observed in patients with fetal-type posterior cerebral artery development than in those without it (28.2% vs. 18.8%, P = 0.035). However, Suzuki stages did not differ between the 2 matched groups (4.03 vs. 4.20, P = 0.081). Hemorrhagic events occurred more frequently in patients with MMD with fetal-type posterior cerebral arteries than in those without.


Investigation of the nature of P-induced male recombination in Drosophila melanogaster.
The present study consists of an investigation of P-induced male recombination in Drosophila melanogaster from a number of perspectives. In an initial set of experiments, male recombination induced by several different P strains was examined on both major autosomes. The ability of these P strains to evoke recombination is striking; in many cases it exceeded that of radiation treatment. Also of interest is the apparent nonrandom chromosomal distribution of P-exchange breakpoints. The data suggest that both recombinagenic capacity and distribution pattern of exchange breakpoints may be P-strain specific. In addition to these findings, we have confirmed previous indications that P-induced exchange is reasonably symmetrical and that it frequently occurs during premeiotic stages of spermatogenesis. Moreover, we have established that radiation and P background act additively with regard to the induction of male recombination. The second part of the work involved an analysis of heterochromatic vs. euchromatic recombination induced by several recombinagenically potent P strains. Results of these experiments have confirmed our earlier findings concerning the recombinagenic capacity of p strains. More importantly, it would appear that P-induced exchange in heterochromatin is rare. The induction of various kinds of mutations was also monitored in several of these experiments. The results indicate that the mutagenic potential of the P strains is substantial and of particular interest, that certain types of mutations are P-strain specific. For example, rare heterochromatic lesions were recovered exclusively in the experiment using the h12 strain, whereas a novel pleiotropic mutation occurred at a high frequency only in the T-007 experiment. Our findings are discussed within the context of a model of P-induced exchange.


Color discrimination testing reveals early printshop solvent neurotoxicity better than a neuropsychological test battery.
Twenty standardized neuropsychological tests were compared to the Lanthony D-15 desaturated panel test of chromotopsia to determine which measures would most effectively discriminate solvent-exposed print workers from controls. All the workers of the printing services of Université du Québec a Montréal (N = 29) were assessed excepted one who refused to participate. Twenty-nine workers (employed on a full time basis) matched for occupation, age, sex, education, vocabulary, and written arithmetic (p >.13) with the print workers served as controls. Air samples revealed exposure to ethanol, perchloroethylene, methyl chloride, xylene, toluene, and stoddard solvent in the print shop. None of the 20 neuropsychological measures yielded a statistically significant decrement in the print workers. On the other hand, the Lanthony D-15 test revealed a significant group difference (p <.01) and a highly significant interaction between job category within the print shop and dyschromatopsia (p <.001) - the graphists, photocopiers, and printers/binders manifesting increasing severity of impairment as a function of increasing magnitude, and/or type, of dose. The results were interpreted to mean that in a cohort of printers with low seniority (10.42 years) such as this one, neuro-opthalmotoxic effects can be observed earlier than putative neuropsychotoxic effects with the tools at hand.


Incorporation of protein into spore coats is not cell autonomous in Dictyostelium.
At maturity, the spores of Dictyostelium are suspended in a viscous fluid droplet, with each spore being surrounded by its own spore coat. Certain glycoproteins characteristic of the spore coat are also dissolved in this fluid matrix after the spore coat is formed. To determine whether any proteins of the coat reside in this fluid phase earlier during the process of spore coat assembly, pairs of strains which differed in a spore coat protein carbohydrate marker were mixed and allowed to form spore coats in each other's presence. We reasoned that proteins belonging to an early, soluble, extracellular pool would be incorporated into the spore coats of both strains. To detect trans-incorporation, spores were labeled with a fluorescent antibody against the carbohydrate marker and each spore's fluorescence was analyzed by flow cytometry. Several proteins of both the outer and inner protein layers of the coat appeared to be faithfully and reciprocally trans-incorporated and hence judged to belong to a soluble, assembly-phase pool. Western blot analysis of sorted spores, and EM localization, confirmed this conclusion. In contrast, one outer-layer protein was not trans-incorporated, and was concluded to be insoluble at the time of secretion. Three classes of spore coat proteins can be described: (a) Insoluble from the time of secretion; (b) present in the early, soluble pool but not the late pool after spore coat formation; and (c) present in the soluble pool throughout spore coat assembly. These classes may, respectively: (a) Nucleate spore coat assembly; (b) comprise a scaffold defining the dimensions of the nascent spore coat; and (c) complete the assembly process by intercalation into the scaffold.


Hybrid one-dimensional nanostructures: one-pot preparation of nanoparticle chains via directed self-assembly of in situ synthesized discrete Au nanoparticles.
The fabrication of well-defined one-dimensional (1D) arrays is becoming a challenge for the development of the next generation of advanced nanodevices. Herein, a simple concept is proposed for the in situ synthesis and self-assembly of gold nanoparticles (AuNPs) into 1D arrays via a one-step process. The results demonstrated the formation of nanoparticle chains (NPC) with high aspect ratio based on discrete Au nanoparticles stabilized by short thiol ligands. A model was proposed to explain the self-assembly based on the investigation of several parameters such as pH, solvent, temperature, and nature of the ligand on the 1D assembly formation. Hydrogen bonding was identified as a key factor to direct the self-assembly of the hybrid organic-inorganic nanomaterials into the well-defined 1D nanostructures. This simple and cost-effective concept could potentially be extended to the fabrication of a variety of hybrid 1D nanostructures possessing unique physical properties leading to a wide range of applications including catalysis, bionanotechnology, nanoelectronics, and photonics.


Quantitation of aberrant interlocus T-cell receptor rearrangements in mouse thymocytes and the effect of the herbicide 2,4-dichlorophenoxyacetic acid.
Small studies in human populations have suggested a correlation between the frequency of errors in antigen receptor gene assembly and lymphoid malignancy risk. In particular, agricultural workers exposed to pesticides have both an increased risk for lymphoma and an increased frequency of errors in antigen receptor gene assembly. In order to further investigate the potential of such errors to serve as a mechanistically based biomarker of lymphoid cancer risk, we have developed a sensitive PCR assay for quantifying errors of V(D)J recombination in the thymocytes of mice. This assay measures interlocus rearrangements between two T-cell receptor loci, V-gamma and J-beta, located on chromosomes 13 and 6, respectively. The baseline frequency in four strains of mice was determined at several ages (2-8 weeks of age) and was found to be stable at approximately 1.5 x 10(-5) per thymocyte. Strain AKR, which has a high susceptibility to T-cell lymphomas, did not show an elevated frequency of aberrant V(D)J events. We used this assay to examine the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the frequency of these events. Female B6C3F1 mice, 27 days of age, were exposed to 2,4-D by gavage at doses of 0, 3, 10, 30, and 100 mg/kg/day for 4 successive days and sacrificed on day 5. Thymus DNA was isolated and examined for illegitimate V(D)J recombination-mediated gene rearrangements. In addition, pregnant mice were exposed to 2,4-D and thymocytes from the offspring examined at 2 weeks of age. No significant increase in aberrant V(D)J rearrangements was found, indicating that under these conditions 2,4-D does not appear to effect this important mechanism of carcinogenesis.